Prophylactic Oophorectomy and breast cancer

Over the past few years, knowledge of genetic susceptibility to breast and ovarian cancer has increased substantially. Testing for mutations in the BRCA1 and BRCA2 genes is becoming increasingly available to women who are believed to have an elevated risk of familial predisposition to breast or ovarian cancer. At the same time, more patients are turning to gynecologists, gynecologic oncologists, and other health care providers for estimates of their own and their daughters' risks of developing ovarian cancer and for information about options for surveillance and prevention.

In discussions of these issues, patients must be provided with information on a well-researched pedigree of the family; risks associated with use of oral contraceptives and hormone replacement therapy; risks of prophylactic oophorectomy; and the possibility that peritoneal carcinoma may develop subsequent to prophylactic oophorectomy.

Indications
Some authors suggest a prophylactic bilateral oophorectomy in patients undergoing hysterectomy or other pelvic surgery to reduce the patient's risk of developing ovarian cancer in the future.

This potential benefit, however, has to be balanced against the long-term risks of estrogen withdrawal, including a possible increased risk of cardiovascular disease and predisposition to osteoporosis. These potential risks are particularly important in patients with breast cancer, in whom exogenous estrogens are usually contraindicated.

Prophylactic oophorectomy is also sometimes considered in women with familial cancer risk. Approximately 10% of ovarian cancers are believed to be familial, and 90% of these hereditary ovarian cancers can be accounted for by mutations in BRCA1 or BRCA2.

Patients with 1 first-degree relative with ovarian cancer have an approximately 5% risk, and patients with 2 first-degree relatives with ovarian cancer have a 7% risk. This risk is considerably higher if a woman tests positive for BRCA1 or BRCA2 mutations-the lifetime risk of ovarian cancer in women who are known to have mutations in BRCA1 or BRCA2 is 15-60%. It is important to counsel such mutation carriers that oophorectomy not only dramatically reduces ovarian cancer risk but also confers a 50% reduction in the incidence of breast cancer in this select group of patients. Women with premenopausal breast cancer who have tested negative for BRCA1 and BRCA2 mutations have a lifetime risk of ovarian cancer of 3-5%. Recent studies have demonstrated that women from so-called breast cancer families without BRCA1 and BRCA2 mutations are most likely not at increased risk for ovarian cancer.

Hereditary ovarian cancers tend to present at an earlier age, but the optimum age at which to perform prophylactic oophorectomy remains unknown. The Gilda Radner Familial Ovarian Cancer Registry recommends oophorectomy when fertility is no longer important to the woman or by the age of 35 years. In the Gynecologic Oncology Center, we recommend that prophylactic oophorectomy be performed 5-10 years earlier than the age when cancer developed in the closest affected relative or by 40 years of age if the patient has finished childbearing.